1,25-dihydroxyvitamin D as a cardiovascular hormone. Effects on calcium current and cytosolic free calcium in vascular smooth muscle cells.

Clinical and in vitro evidence suggests a role for the calcium regulating hormone, 1,25-dihydroxyvitamin D (1,25D) in human and experimental hypertension. To establish the cellular basis for this association, we utilized the whole-cell version of the patch clamp method and fluorescence spectroscopic techniques to measure voltage-dependent calcium channel activity and cytosolic free calcium concentrations ([Ca2+]i) in rat tail artery-derived smooth muscle cells, before and after the addition of 1,25D. 1,25D significantly increased the calcium channel current over the range of test pulses, from -40 to +60 mV, in a dose- and time-dependent manner, appearing by 5 to 10 min of exposure, with maximum effects by 15 min. At 10 and 30 nmol/L, the current increased to 149 +/- 10% and 221 +/- 13% of basal activity of 37.75 +/- 7.7 pA and 37.7 +/- 4.5 pA, respectively. Similarly, at 10 and 100 nmol/L, 1,25D increased cytosolic free calcium levels 115 +/- 2% and 171 +/- 11%, from basal values of 99 +/- 32 nmol/L and 116 +/- 10 nmol/L, respectively. These effects of [Ca2+]i developed slowly over 3 to 4 min. Peak values were achieved by 30 min of incubation and were reversible with removal of 1,25D from the medium. Altogether, these direct effects of 1,25D on calcium current and [Ca2+]i in vascular smooth muscle cells support a role for 1,25D in vascular physiology, and provide a cellular basis for better understanding the involvement of 1,25D in hypertensive vascular disease.